January 09, 2020
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FDA approves Ayvakit for unresectable, metastatic gastrointestinal stromal tumors harboring rare mutation

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Richard Pazdur
Richard Pazdur

The FDA today approved avapritinib for the treatment of adults with unresectable or metastatic gastrointestinal stromal tumors that harbor a platelet-derived growth factor receptor alpha, or PDGFRA, exon 18 mutation.

This approval — which includes gastrointestinal stromal tumors (GIST) with PDGFRA D842V mutation, the most common exon 18 mutation — marks the first of a targeted therapy to treat this rare mutation in these tumors. Up to about 10% of patients with GIST harbor a PDGFRA mutation.

GIST harboring a PDGFRA exon 18 mutation do not respond to standard therapies for GIST. However, today’s approval provides patients with the first drug specifically approved for GIST harboring this mutation,” Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research, said in a press release. “Clinical trials showed a high response rate, with almost 85% of patients experiencing tumor shrinkage with this targeted drug.”

The approval of avapritinib (Ayvakit, Blueprint Medicines Corp.), a kinase inhibitor, was based on data from a trial of 43 patients with GIST and a PDGFRA exon 18 mutation, including 38 with a PDGFRA D842V mutation. Patients received 300 mg or 400 mg avapritinib daily until disease progression or unacceptable toxicity.

Researchers reported an overall response rate of 84%, which included a 7% complete response rate and 77% partial response rate.

Among those with a PDGFRA D842V mutation, the ORR reached 89%, with an 8% complete response rate and 82% partial response rate.

Sixty-one percent of responding patients with an exon 18 mutation had a response that lasted for at least 6 months, and median duration of response had not been reached.

Adverse events associated with avapritinib included edema, nausea, fatigue/asthenia, cognitive impairment, vomiting, decreased appetite, diarrhea, hair color changes, increase lacrimation, abdominal pain, constipation, rash and dizziness.

Avapritinib received orphan drug, breakthrough therapy and fast track designations for this indication.